Danegaptide/ZP1609



Danegaptide/ZP1609

Danegaptide (ZP1609/GAP-134), a small modified dipeptide, has been identified as a potent and selective second generation gap junction modifier with oral bioavailability.

Gap-junctions are specialized pores that ensure the coordinated transmission of electrical impulses from cell to cell across the heart. This spreading is essential for synchronized contraction of the heart. During a heart attack (acute myocardial infarction) or during chronic heart disease gap-junction pores close, which inhibit spreading of electrical impulses. As a result, electrical impulses take atypical routes which may lead to irregular heart beats, or arrhythmias, and death.  Using pre-clinical animal models, we demonstrated that our first generation gap junction modifier rotigaptide specifically inhibits the re-entry arrhythmia mechanism by normalizing the electrical conduction in the heart and preventing life-threatening arrhythmias during these conditions.  

Zealand Pharma entered into a Research Collaboration and License Agreement with Wyeth (now a subsidiary of Pfizer) in April 2003 to co-develop, manufacture and market rotigaptide, a first-generation gap junction modulator. In February 2004, the agreement was extended to cover new collaborative activities relating to all Zealand Pharma gap-junction modulators. From this collaboration, Zealand Pharma and Wyeth identified danegaptide, a small modified dipeptide, as a potent and selective second-generation gap junction modifier with oral availability. Following the identification of danegaptide, further development of rotigaptide was terminated.

The clinical Phase I program for danegaptide conducted by Wyeth included both an intravenous formulation for acute use and an oral formulation for long-term use for prevention of post-operating AF. Following the acquisition of Wyeth by Pfizer in 2009, Wyeth’s active development of danegaptide was halted. Pfizer had previously announced that it was ceasing all development in the cardiovascular area. Danegaptide has now been fully returned to Zealand. Zealand Pharma aims to continue development of Danegaptide together with a future partner.

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